Locus coeruleus to basolateral amygdala noradrenergic projections promote anxiety-like behavior

Increased tonic activity of locus coeruleus noradrenergic (LC-NE) neurons induces anxiety-like and aversive behavior. While some information is known about the afferent circuitry that endogenously drives this neural activity and behavior, the downstream receptors and anatomical projections that mediate these acute risk aversive behavioral states via the LC-NE system remain unresolved. Here we use a combination of retrograde tracing, fast-scan cyclic voltammetry, electrophysiology, and in vivo optogenetics with localized pharmacology to identify neural substrates downstream of increased tonic LC-NE activity in mice. We demonstrate that photostimulation of LC-NE fibers in the BLA evokes norepinephrine release in the basolateral amygdala (BLA), alters BLA neuronal activity, conditions aversion, and increases anxiety-like behavior. Additionally, we report that β-adrenergic receptors mediate the anxiety-like phenotype of increased NE release in the BLA. These studies begin to illustrate how the complex efferent system of the LC-NE system selectively mediates behavior through distinct receptor and projection-selective mechanisms

Phosphorylation of pRb: mechanism for RB pathway inactivation in MYCN-amplified retinoblastoma.

A small, but unique subgroup of retinoblastoma has been identified with no detectable mutation in the retinoblastoma gene (RB1) and with high levels of MYCN gene amplification. This manuscript investigated alternate pathways of inactivating pRb, the encoded protein in these tumors. We analyzed the mutation status of the RB1 gene and MYCN copy number in a series of 245 unilateral retinoblastomas, and the phosphorylation status of pRb in a subset of five tumors using immunohistochemistry. There were 203 tumors with two mutations in RB1 (RB1(-/-) , 83%), 29 with one (RB1(+/-) , 12%) and 13 with no detectable mutations (RB1(+/+) , 5%). Eighteen tumors carried MYCN amplification between 29 and 110 copies: 12 had two (RB1(-/-) ) or one RB1 (RB1(+/-) ) mutations, while six had no mutations (RB1(+/+) ). Immunohistochemical staining of tumor sections with antibodies against pRb and phosphorylated Rb (ppRb) displayed high levels of pRb and ppRb in both RB1(+/+) and RB1(+/-) tumors with MYCN amplification compared to no expression of these proteins in a classic RB1(-/-) , MYCN-low tumor. These results establish that high MYCN amplification can be present in retinoblastoma with or without coding sequence mutations in the RB1 gene. The functional state of pRb is inferred to be inactive due to phosphorylation of pRb in the MYCN-amplified retinoblastoma without coding sequence mutations. This makes inactivation of RB1 by gene mutation or its protein product, pRb, by protein phosphorylation, a necessary condition for initiating retinoblastoma tumorigenesis, independent of MYCN amplification

Self-assembled nanoparticles as multifunctional drugs for anti-microbial therapies

crosscheck: This document is CrossCheck deposited related_data: Supplementary Information copyright_licence: The Royal Society of Chemistry has an exclusive publication licence for this journal copyright_licence: The accepted version of this article will be made freely available after a 12 month embargo period history: Received 15 January 2014; Accepted 22 May 2014; Accepted Manuscript published 22 May 2014; Advance Article published 4 June 2014; Version of Record published 19 June 201

Searching for Multijet Resonances at the LHC

Recently it was shown that there is a class of models in which colored vector and scalar resonances can be copiously produced at the Tevatron with decays to multijet final states, consistent with all experimental constraints and having strong discovery potential. We investigate the collider phenomenology of TeV scale colored resonances at the LHC and demonstrate a strong discovery potential for the scalars with early data as well as the vectors with additional statistics. We argue that the signal can be self-calibrating and using this fact we propose a search strategy which we show to be robust to systematic errors typically expected from Monte Carlo background estimates. We model the resonances with a phenomenological Lagrangian that describes them as bound states of colored vectorlike fermions due to new confining gauge interactions. However, the phenomenological Lagrangian treatment is quite general and can represent other scenarios of microscopic physics as well.Comment: 28 pages, 13 figures, pdflatex. Discussion of background expanded, minor modifications made. Version to appear in JHE

HAT-P-56b: An inflated massive Hot Jupiter transiting a bright F star followed up with K2 Campaign 0 observations

We report the discovery of HAT-P-56b by the HATNet survey, an inflated hot Jupiter transiting a bright F type star in Field 0 of NASA's K2 mission. We combine ground-based discovery and follow-up light curves with high precision photometry from K2, as well as ground-based radial velocities from TRES on the FLWO 1.5m telescope to determine the physical properties of this system. HAT-P-56b has a mass of $2.18 M_J$, radius of $1.47 R_J$, and transits its host star on a near-grazing orbit with a period of 2.7908 d. The radius of HAT-P-56b is among the largest known for a planet with $M_p > 2 M_J$. The host star has a V-band magnitude of 10.9, mass of 1.30 $M_\odot$, and radius of 1.43 $R_\odot$. The periodogram of the K2 light curve suggests the star is a $\gamma$ Dor variable. HAT-P-56b is an example of a ground-based discovery of a transiting planet, where space-based observations greatly improve the confidence in the confirmation of its planetary nature, and also improve the accuracy of the planetary parameters.Comment: 13 pages, 11 figures, accepted by A

Conserved Quantities in f(R)f(R) Gravity via Noether Symmetry

This paper is devoted to investigate $f(R)$ gravity using Noether symmetry approach. For this purpose, we consider Friedmann Robertson-Walker (FRW) universe and spherically symmetric spacetimes. The Noether symmetry generators are evaluated for some specific choice of $f(R)$ models in the presence of gauge term. Further, we calculate the corresponding conserved quantities in each case. Moreover, the importance and stability criteria of these models are discussed.Comment: 14 pages, accepted for publication in Chin. Phys. Let